EULAR (European League Against Rheumatism): 2011 Congress

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – Use of canakinumab led to greater reductions in pain among patients with acute gouty arthritis flares after 3 days, and superior prevention of new flares during 12 weeks of follow-up, compared with triamcinolone acetonide in a pair of phase III trials that together enrolled 456 patients.

"Canakinumab is a potential new therapeutic option for acute flares in frequently flaring gouty arthritis patients with limited treatment options," Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

Canakinumab is a fully human monoclonal antibody to interleukin (IL)-1 beta that selectively binds to and inhibits the proinflammatory molecule IL-1 beta, and already has Food and Drug Administration approval for treating CAPS (cryopyrin-associated periodic syndromes).

Based in part on the efficacy and safety data from the two reported phase III trials, Novartis, the company the markets canakinumab (Ilaris), filed an application with the FDA earlier this year for a supplemental indication for treating gouty arthritis flares. The FDA’s Arthritis Advisory Committee plans to discuss this application on June 21.

In the two new gouty arthritis trials, canakinumab’s safety profile during the first 12 weeks of treatment "appeared consistent with longer-term safety data from CAPS patients; there were no safety signals related to specific organ class," said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at the Robert Wood Johnson Medical School in New Brunswick, N.J. The most notable safety observation she made from the new results centered on "a modest increase in infections, mostly mild to moderate, with no opportunistic infections reported," she said.

Despite this promising safety and efficacy, one expert viewed canakinumab as an agent for a "niche population, patients [with gout] who flare and you can’t do anything about it" using standard drugs, commented Dr. Dinesh Khanna, a rheumatologist specializing in gout at the University of California, Los Angeles.

Goutologists see a lot of patients with diabetes, kidney disease, and hypertension who can’t take NSAIDs or colchicine. "You also can’t give them a steroid monthly, so these patients flare because of their high uric acid level and you’re stuck. These are the patients who can be treated with an anti-IL-1 beta to prevent gout attacks," he said in an interview.

The Beta-RELIEVED (Response in Acute Flare and in Prevention of Episodes of Reflare in Gout) and Beta-RELIEVED II trials enrolled patients within 5 days of an acute flare of gouty arthritis who had at least three flares during the prior year and were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine. All patients met the American College of Rheumatology’s diagnostic criteria for gouty arthritis, and had pain intensity of at least 50 mm on a visual analog scale of 0–100 mm.

The researchers randomized patients to receive a subcutaneous injection of 150-mg canakinumab or an intramuscular injection of 40-mg triamcinolone acetonide. Patients who reflared during the subsequent 12 weeks during the first phase of the study qualified to receive an additional dose of their assigned drug with each flare.

The study had two primary end points. One was pain resolution at 72 hours after initial treatment. At that time, patients who were treated with canakinumab in the Beta-RELIEVED study had an average pain score that was 11 mm lower than that of patients in the comparator group, a statistically significant difference, reported Dr. Alexander So, a coinvestigator on the study and professor of rheumatology at the University of Lausanne (Switzerland).

Patients who were treated with canakinumab began to show significantly better pain reduction, compared with those who got triamcinolone within 12 hours after their first dose, and the advantage in pain relief continued each time the investigators measured pain during the first 7 days after treatment, Dr. So said. Neither Dr. So nor Dr. Schlesinger reported the results for this end point from the Beta-RELIEVED II trial.

The second primary end point was the percentage of patients having new flares during the first 12 weeks following their initial therapy. In the Beta-RELIEVED trial, 19% of the 115 patients who were treated with canakinumab and 37% of the 115 patients treated with triamcinolone had a new flare, a 55% relative risk reduction with canakinumab that was statistically significant. In the second trial, canakinumab use led to a 68% relative reduction in new flares, also a statistically significant difference in the study that randomized 226 patients, Dr. Schlesinger reported.

The canakinumab-treated patients also showed other signs of superior response in several secondary efficacy measures. Patients in the canakinumab group had a significant reduction in their mean number of flares, significantly less inflammation and swelling, and better suppression of inflammatory markers after 12 weeks, the researchers said.

In the safety analysis, canakinumab was associated with similar rates of all adverse events, a similar low rate of serious adverse events, and a similar low rate of adverse events leading to discontinuation, compared with patients who received triamcinolone.

The Beta-RELIEVED trials were sponsored by Novartis, which markets canakinumab (Ilaris). Dr. Schlesinger said that she is a on the advisory board of Novartis, Enzyme Rx, Takeda, URL Pharma, and Savient. She is a consultant to and has received research grants from Novartis, and is on the speakers bureau of Takeda and Savient. Dr. So said that he is a consultant to Novartis, Bristol-Myers Squibb, Merck, Pfizer, and UCB Pharma. Dr. Khanna said that he is a consultant to Novartis, Takeda, Savient, and UCB Pharma.

LONDON – Use of canakinumab led to greater reductions in pain among patients with acute gouty arthritis flares after 3 days, and superior prevention of new flares during 12 weeks of follow-up, compared with triamcinolone acetonide in a pair of phase III trials that together enrolled 456 patients.

"Canakinumab is a potential new therapeutic option for acute flares in frequently flaring gouty arthritis patients with limited treatment options," Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

Canakinumab is a fully human monoclonal antibody to interleukin (IL)-1 beta that selectively binds to and inhibits the proinflammatory molecule IL-1 beta, and already has Food and Drug Administration approval for treating CAPS (cryopyrin-associated periodic syndromes).

Based in part on the efficacy and safety data from the two reported phase III trials, Novartis, the company the markets canakinumab (Ilaris), filed an application with the FDA earlier this year for a supplemental indication for treating gouty arthritis flares. The FDA’s Arthritis Advisory Committee plans to discuss this application on June 21.

In the two new gouty arthritis trials, canakinumab’s safety profile during the first 12 weeks of treatment "appeared consistent with longer-term safety data from CAPS patients; there were no safety signals related to specific organ class," said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at the Robert Wood Johnson Medical School in New Brunswick, N.J. The most notable safety observation she made from the new results centered on "a modest increase in infections, mostly mild to moderate, with no opportunistic infections reported," she said.

Despite this promising safety and efficacy, one expert viewed canakinumab as an agent for a "niche population, patients [with gout] who flare and you can’t do anything about it" using standard drugs, commented Dr. Dinesh Khanna, a rheumatologist specializing in gout at the University of California, Los Angeles.

Goutologists see a lot of patients with diabetes, kidney disease, and hypertension who can’t take NSAIDs or colchicine. "You also can’t give them a steroid monthly, so these patients flare because of their high uric acid level and you’re stuck. These are the patients who can be treated with an anti-IL-1 beta to prevent gout attacks," he said in an interview.

The Beta-RELIEVED (Response in Acute Flare and in Prevention of Episodes of Reflare in Gout) and Beta-RELIEVED II trials enrolled patients within 5 days of an acute flare of gouty arthritis who had at least three flares during the prior year and were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine. All patients met the American College of Rheumatology’s diagnostic criteria for gouty arthritis, and had pain intensity of at least 50 mm on a visual analog scale of 0–100 mm.

The researchers randomized patients to receive a subcutaneous injection of 150-mg canakinumab or an intramuscular injection of 40-mg triamcinolone acetonide. Patients who reflared during the subsequent 12 weeks during the first phase of the study qualified to receive an additional dose of their assigned drug with each flare.

The study had two primary end points. One was pain resolution at 72 hours after initial treatment. At that time, patients who were treated with canakinumab in the Beta-RELIEVED study had an average pain score that was 11 mm lower than that of patients in the comparator group, a statistically significant difference, reported Dr. Alexander So, a coinvestigator on the study and professor of rheumatology at the University of Lausanne (Switzerland).

Patients who were treated with canakinumab began to show significantly better pain reduction, compared with those who got triamcinolone within 12 hours after their first dose, and the advantage in pain relief continued each time the investigators measured pain during the first 7 days after treatment, Dr. So said. Neither Dr. So nor Dr. Schlesinger reported the results for this end point from the Beta-RELIEVED II trial.

The second primary end point was the percentage of patients having new flares during the first 12 weeks following their initial therapy. In the Beta-RELIEVED trial, 19% of the 115 patients who were treated with canakinumab and 37% of the 115 patients treated with triamcinolone had a new flare, a 55% relative risk reduction with canakinumab that was statistically significant. In the second trial, canakinumab use led to a 68% relative reduction in new flares, also a statistically significant difference in the study that randomized 226 patients, Dr. Schlesinger reported.

The canakinumab-treated patients also showed other signs of superior response in several secondary efficacy measures. Patients in the canakinumab group had a significant reduction in their mean number of flares, significantly less inflammation and swelling, and better suppression of inflammatory markers after 12 weeks, the researchers said.

In the safety analysis, canakinumab was associated with similar rates of all adverse events, a similar low rate of serious adverse events, and a similar low rate of adverse events leading to discontinuation, compared with patients who received triamcinolone.

The Beta-RELIEVED trials were sponsored by Novartis, which markets canakinumab (Ilaris). Dr. Schlesinger said that she is a on the advisory board of Novartis, Enzyme Rx, Takeda, URL Pharma, and Savient. She is a consultant to and has received research grants from Novartis, and is on the speakers bureau of Takeda and Savient. Dr. So said that he is a consultant to Novartis, Bristol-Myers Squibb, Merck, Pfizer, and UCB Pharma. Dr. Khanna said that he is a consultant to Novartis, Takeda, Savient, and UCB Pharma.

LONDON – Use of canakinumab led to greater reductions in pain among patients with acute gouty arthritis flares after 3 days, and superior prevention of new flares during 12 weeks of follow-up, compared with triamcinolone acetonide in a pair of phase III trials that together enrolled 456 patients.

"Canakinumab is a potential new therapeutic option for acute flares in frequently flaring gouty arthritis patients with limited treatment options," Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

Canakinumab is a fully human monoclonal antibody to interleukin (IL)-1 beta that selectively binds to and inhibits the proinflammatory molecule IL-1 beta, and already has Food and Drug Administration approval for treating CAPS (cryopyrin-associated periodic syndromes).

Based in part on the efficacy and safety data from the two reported phase III trials, Novartis, the company the markets canakinumab (Ilaris), filed an application with the FDA earlier this year for a supplemental indication for treating gouty arthritis flares. The FDA’s Arthritis Advisory Committee plans to discuss this application on June 21.

In the two new gouty arthritis trials, canakinumab’s safety profile during the first 12 weeks of treatment "appeared consistent with longer-term safety data from CAPS patients; there were no safety signals related to specific organ class," said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at the Robert Wood Johnson Medical School in New Brunswick, N.J. The most notable safety observation she made from the new results centered on "a modest increase in infections, mostly mild to moderate, with no opportunistic infections reported," she said.

Despite this promising safety and efficacy, one expert viewed canakinumab as an agent for a "niche population, patients [with gout] who flare and you can’t do anything about it" using standard drugs, commented Dr. Dinesh Khanna, a rheumatologist specializing in gout at the University of California, Los Angeles.

Goutologists see a lot of patients with diabetes, kidney disease, and hypertension who can’t take NSAIDs or colchicine. "You also can’t give them a steroid monthly, so these patients flare because of their high uric acid level and you’re stuck. These are the patients who can be treated with an anti-IL-1 beta to prevent gout attacks," he said in an interview.

The Beta-RELIEVED (Response in Acute Flare and in Prevention of Episodes of Reflare in Gout) and Beta-RELIEVED II trials enrolled patients within 5 days of an acute flare of gouty arthritis who had at least three flares during the prior year and were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine. All patients met the American College of Rheumatology’s diagnostic criteria for gouty arthritis, and had pain intensity of at least 50 mm on a visual analog scale of 0–100 mm.

The researchers randomized patients to receive a subcutaneous injection of 150-mg canakinumab or an intramuscular injection of 40-mg triamcinolone acetonide. Patients who reflared during the subsequent 12 weeks during the first phase of the study qualified to receive an additional dose of their assigned drug with each flare.

The study had two primary end points. One was pain resolution at 72 hours after initial treatment. At that time, patients who were treated with canakinumab in the Beta-RELIEVED study had an average pain score that was 11 mm lower than that of patients in the comparator group, a statistically significant difference, reported Dr. Alexander So, a coinvestigator on the study and professor of rheumatology at the University of Lausanne (Switzerland).

Patients who were treated with canakinumab began to show significantly better pain reduction, compared with those who got triamcinolone within 12 hours after their first dose, and the advantage in pain relief continued each time the investigators measured pain during the first 7 days after treatment, Dr. So said. Neither Dr. So nor Dr. Schlesinger reported the results for this end point from the Beta-RELIEVED II trial.

The second primary end point was the percentage of patients having new flares during the first 12 weeks following their initial therapy. In the Beta-RELIEVED trial, 19% of the 115 patients who were treated with canakinumab and 37% of the 115 patients treated with triamcinolone had a new flare, a 55% relative risk reduction with canakinumab that was statistically significant. In the second trial, canakinumab use led to a 68% relative reduction in new flares, also a statistically significant difference in the study that randomized 226 patients, Dr. Schlesinger reported.

The canakinumab-treated patients also showed other signs of superior response in several secondary efficacy measures. Patients in the canakinumab group had a significant reduction in their mean number of flares, significantly less inflammation and swelling, and better suppression of inflammatory markers after 12 weeks, the researchers said.

In the safety analysis, canakinumab was associated with similar rates of all adverse events, a similar low rate of serious adverse events, and a similar low rate of adverse events leading to discontinuation, compared with patients who received triamcinolone.

The Beta-RELIEVED trials were sponsored by Novartis, which markets canakinumab (Ilaris). Dr. Schlesinger said that she is a on the advisory board of Novartis, Enzyme Rx, Takeda, URL Pharma, and Savient. She is a consultant to and has received research grants from Novartis, and is on the speakers bureau of Takeda and Savient. Dr. So said that he is a consultant to Novartis, Bristol-Myers Squibb, Merck, Pfizer, and UCB Pharma. Dr. Khanna said that he is a consultant to Novartis, Takeda, Savient, and UCB Pharma.

LONDON – Use of canakinumab led to greater reductions in pain among patients with acute gouty arthritis flares after 3 days, and superior prevention of new flares during 12 weeks of follow-up, compared with triamcinolone acetonide in a pair of phase III trials that together enrolled 456 patients.

"Canakinumab is a potential new therapeutic option for acute flares in frequently flaring gouty arthritis patients with limited treatment options," Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

Canakinumab is a fully human monoclonal antibody to interleukin (IL)-1 beta that selectively binds to and inhibits the proinflammatory molecule IL-1 beta, and already has Food and Drug Administration approval for treating CAPS (cryopyrin-associated periodic syndromes).

Based in part on the efficacy and safety data from the two reported phase III trials, Novartis, the company the markets canakinumab (Ilaris), filed an application with the FDA earlier this year for a supplemental indication for treating gouty arthritis flares. The FDA’s Arthritis Advisory Committee plans to discuss this application on June 21.

In the two new gouty arthritis trials, canakinumab’s safety profile during the first 12 weeks of treatment "appeared consistent with longer-term safety data from CAPS patients; there were no safety signals related to specific organ class," said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at the Robert Wood Johnson Medical School in New Brunswick, N.J. The most notable safety observation she made from the new results centered on "a modest increase in infections, mostly mild to moderate, with no opportunistic infections reported," she said.

Despite this promising safety and efficacy, one expert viewed canakinumab as an agent for a "niche population, patients [with gout] who flare and you can’t do anything about it" using standard drugs, commented Dr. Dinesh Khanna, a rheumatologist specializing in gout at the University of California, Los Angeles.

Goutologists see a lot of patients with diabetes, kidney disease, and hypertension who can’t take NSAIDs or colchicine. "You also can’t give them a steroid monthly, so these patients flare because of their high uric acid level and you’re stuck. These are the patients who can be treated with an anti-IL-1 beta to prevent gout attacks," he said in an interview.

The Beta-RELIEVED (Response in Acute Flare and in Prevention of Episodes of Reflare in Gout) and Beta-RELIEVED II trials enrolled patients within 5 days of an acute flare of gouty arthritis who had at least three flares during the prior year and were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine. All patients met the American College of Rheumatology’s diagnostic criteria for gouty arthritis, and had pain intensity of at least 50 mm on a visual analog scale of 0–100 mm.

The researchers randomized patients to receive a subcutaneous injection of 150-mg canakinumab or an intramuscular injection of 40-mg triamcinolone acetonide. Patients who reflared during the subsequent 12 weeks during the first phase of the study qualified to receive an additional dose of their assigned drug with each flare.

The study had two primary end points. One was pain resolution at 72 hours after initial treatment. At that time, patients who were treated with canakinumab in the Beta-RELIEVED study had an average pain score that was 11 mm lower than that of patients in the comparator group, a statistically significant difference, reported Dr. Alexander So, a coinvestigator on the study and professor of rheumatology at the University of Lausanne (Switzerland).

Patients who were treated with canakinumab began to show significantly better pain reduction, compared with those who got triamcinolone within 12 hours after their first dose, and the advantage in pain relief continued each time the investigators measured pain during the first 7 days after treatment, Dr. So said. Neither Dr. So nor Dr. Schlesinger reported the results for this end point from the Beta-RELIEVED II trial.

The second primary end point was the percentage of patients having new flares during the first 12 weeks following their initial therapy. In the Beta-RELIEVED trial, 19% of the 115 patients who were treated with canakinumab and 37% of the 115 patients treated with triamcinolone had a new flare, a 55% relative risk reduction with canakinumab that was statistically significant. In the second trial, canakinumab use led to a 68% relative reduction in new flares, also a statistically significant difference in the study that randomized 226 patients, Dr. Schlesinger reported.

The canakinumab-treated patients also showed other signs of superior response in several secondary efficacy measures. Patients in the canakinumab group had a significant reduction in their mean number of flares, significantly less inflammation and swelling, and better suppression of inflammatory markers after 12 weeks, the researchers said.

In the safety analysis, canakinumab was associated with similar rates of all adverse events, a similar low rate of serious adverse events, and a similar low rate of adverse events leading to discontinuation, compared with patients who received triamcinolone.

The Beta-RELIEVED trials were sponsored by Novartis, which markets canakinumab (Ilaris). Dr. Schlesinger said that she is a on the advisory board of Novartis, Enzyme Rx, Takeda, URL Pharma, and Savient. She is a consultant to and has received research grants from Novartis, and is on the speakers bureau of Takeda and Savient. Dr. So said that he is a consultant to Novartis, Bristol-Myers Squibb, Merck, Pfizer, and UCB Pharma. Dr. Khanna said that he is a consultant to Novartis, Takeda, Savient, and UCB Pharma.

LONDON – Use of canakinumab led to greater reductions in pain among patients with acute gouty arthritis flares after 3 days, and superior prevention of new flares during 12 weeks of follow-up, compared with triamcinolone acetonide in a pair of phase III trials that together enrolled 456 patients.

"Canakinumab is a potential new therapeutic option for acute flares in frequently flaring gouty arthritis patients with limited treatment options," Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

Canakinumab is a fully human monoclonal antibody to interleukin (IL)-1 beta that selectively binds to and inhibits the proinflammatory molecule IL-1 beta, and already has Food and Drug Administration approval for treating CAPS (cryopyrin-associated periodic syndromes).

Based in part on the efficacy and safety data from the two reported phase III trials, Novartis, the company the markets canakinumab (Ilaris), filed an application with the FDA earlier this year for a supplemental indication for treating gouty arthritis flares. The FDA’s Arthritis Advisory Committee plans to discuss this application on June 21.

In the two new gouty arthritis trials, canakinumab’s safety profile during the first 12 weeks of treatment "appeared consistent with longer-term safety data from CAPS patients; there were no safety signals related to specific organ class," said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at the Robert Wood Johnson Medical School in New Brunswick, N.J. The most notable safety observation she made from the new results centered on "a modest increase in infections, mostly mild to moderate, with no opportunistic infections reported," she said.

Despite this promising safety and efficacy, one expert viewed canakinumab as an agent for a "niche population, patients [with gout] who flare and you can’t do anything about it" using standard drugs, commented Dr. Dinesh Khanna, a rheumatologist specializing in gout at the University of California, Los Angeles.

Goutologists see a lot of patients with diabetes, kidney disease, and hypertension who can’t take NSAIDs or colchicine. "You also can’t give them a steroid monthly, so these patients flare because of their high uric acid level and you’re stuck. These are the patients who can be treated with an anti-IL-1 beta to prevent gout attacks," he said in an interview.

The Beta-RELIEVED (Response in Acute Flare and in Prevention of Episodes of Reflare in Gout) and Beta-RELIEVED II trials enrolled patients within 5 days of an acute flare of gouty arthritis who had at least three flares during the prior year and were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine. All patients met the American College of Rheumatology’s diagnostic criteria for gouty arthritis, and had pain intensity of at least 50 mm on a visual analog scale of 0–100 mm.

The researchers randomized patients to receive a subcutaneous injection of 150-mg canakinumab or an intramuscular injection of 40-mg triamcinolone acetonide. Patients who reflared during the subsequent 12 weeks during the first phase of the study qualified to receive an additional dose of their assigned drug with each flare.

The study had two primary end points. One was pain resolution at 72 hours after initial treatment. At that time, patients who were treated with canakinumab in the Beta-RELIEVED study had an average pain score that was 11 mm lower than that of patients in the comparator group, a statistically significant difference, reported Dr. Alexander So, a coinvestigator on the study and professor of rheumatology at the University of Lausanne (Switzerland).

Patients who were treated with canakinumab began to show significantly better pain reduction, compared with those who got triamcinolone within 12 hours after their first dose, and the advantage in pain relief continued each time the investigators measured pain during the first 7 days after treatment, Dr. So said. Neither Dr. So nor Dr. Schlesinger reported the results for this end point from the Beta-RELIEVED II trial.

The second primary end point was the percentage of patients having new flares during the first 12 weeks following their initial therapy. In the Beta-RELIEVED trial, 19% of the 115 patients who were treated with canakinumab and 37% of the 115 patients treated with triamcinolone had a new flare, a 55% relative risk reduction with canakinumab that was statistically significant. In the second trial, canakinumab use led to a 68% relative reduction in new flares, also a statistically significant difference in the study that randomized 226 patients, Dr. Schlesinger reported.

The canakinumab-treated patients also showed other signs of superior response in several secondary efficacy measures. Patients in the canakinumab group had a significant reduction in their mean number of flares, significantly less inflammation and swelling, and better suppression of inflammatory markers after 12 weeks, the researchers said.

In the safety analysis, canakinumab was associated with similar rates of all adverse events, a similar low rate of serious adverse events, and a similar low rate of adverse events leading to discontinuation, compared with patients who received triamcinolone.

The Beta-RELIEVED trials were sponsored by Novartis, which markets canakinumab (Ilaris). Dr. Schlesinger said that she is a on the advisory board of Novartis, Enzyme Rx, Takeda, URL Pharma, and Savient. She is a consultant to and has received research grants from Novartis, and is on the speakers bureau of Takeda and Savient. Dr. So said that he is a consultant to Novartis, Bristol-Myers Squibb, Merck, Pfizer, and UCB Pharma. Dr. Khanna said that he is a consultant to Novartis, Takeda, Savient, and UCB Pharma.

LONDON – Use of canakinumab led to greater reductions in pain among patients with acute gouty arthritis flares after 3 days, and superior prevention of new flares during 12 weeks of follow-up, compared with triamcinolone acetonide in a pair of phase III trials that together enrolled 456 patients.

"Canakinumab is a potential new therapeutic option for acute flares in frequently flaring gouty arthritis patients with limited treatment options," Dr. Naomi Schlesinger said at the annual European Congress of Rheumatology.

Canakinumab is a fully human monoclonal antibody to interleukin (IL)-1 beta that selectively binds to and inhibits the proinflammatory molecule IL-1 beta, and already has Food and Drug Administration approval for treating CAPS (cryopyrin-associated periodic syndromes).

Based in part on the efficacy and safety data from the two reported phase III trials, Novartis, the company the markets canakinumab (Ilaris), filed an application with the FDA earlier this year for a supplemental indication for treating gouty arthritis flares. The FDA’s Arthritis Advisory Committee plans to discuss this application on June 21.

In the two new gouty arthritis trials, canakinumab’s safety profile during the first 12 weeks of treatment "appeared consistent with longer-term safety data from CAPS patients; there were no safety signals related to specific organ class," said Dr. Schlesinger, chief of the division of rheumatology and connective tissue research at the Robert Wood Johnson Medical School in New Brunswick, N.J. The most notable safety observation she made from the new results centered on "a modest increase in infections, mostly mild to moderate, with no opportunistic infections reported," she said.

Despite this promising safety and efficacy, one expert viewed canakinumab as an agent for a "niche population, patients [with gout] who flare and you can’t do anything about it" using standard drugs, commented Dr. Dinesh Khanna, a rheumatologist specializing in gout at the University of California, Los Angeles.

Goutologists see a lot of patients with diabetes, kidney disease, and hypertension who can’t take NSAIDs or colchicine. "You also can’t give them a steroid monthly, so these patients flare because of their high uric acid level and you’re stuck. These are the patients who can be treated with an anti-IL-1 beta to prevent gout attacks," he said in an interview.

The Beta-RELIEVED (Response in Acute Flare and in Prevention of Episodes of Reflare in Gout) and Beta-RELIEVED II trials enrolled patients within 5 days of an acute flare of gouty arthritis who had at least three flares during the prior year and were contraindicated for, intolerant of, or unresponsive to NSAIDs and colchicine. All patients met the American College of Rheumatology’s diagnostic criteria for gouty arthritis, and had pain intensity of at least 50 mm on a visual analog scale of 0–100 mm.

The researchers randomized patients to receive a subcutaneous injection of 150-mg canakinumab or an intramuscular injection of 40-mg triamcinolone acetonide. Patients who reflared during the subsequent 12 weeks during the first phase of the study qualified to receive an additional dose of their assigned drug with each flare.

The study had two primary end points. One was pain resolution at 72 hours after initial treatment. At that time, patients who were treated with canakinumab in the Beta-RELIEVED study had an average pain score that was 11 mm lower than that of patients in the comparator group, a statistically significant difference, reported Dr. Alexander So, a coinvestigator on the study and professor of rheumatology at the University of Lausanne (Switzerland).

Patients who were treated with canakinumab began to show significantly better pain reduction, compared with those who got triamcinolone within 12 hours after their first dose, and the advantage in pain relief continued each time the investigators measured pain during the first 7 days after treatment, Dr. So said. Neither Dr. So nor Dr. Schlesinger reported the results for this end point from the Beta-RELIEVED II trial.

The second primary end point was the percentage of patients having new flares during the first 12 weeks following their initial therapy. In the Beta-RELIEVED trial, 19% of the 115 patients who were treated with canakinumab and 37% of the 115 patients treated with triamcinolone had a new flare, a 55% relative risk reduction with canakinumab that was statistically significant. In the second trial, canakinumab use led to a 68% relative reduction in new flares, also a statistically significant difference in the study that randomized 226 patients, Dr. Schlesinger reported.

The canakinumab-treated patients also showed other signs of superior response in several secondary efficacy measures. Patients in the canakinumab group had a significant reduction in their mean number of flares, significantly less inflammation and swelling, and better suppression of inflammatory markers after 12 weeks, the researchers said.

In the safety analysis, canakinumab was associated with similar rates of all adverse events, a similar low rate of serious adverse events, and a similar low rate of adverse events leading to discontinuation, compared with patients who received triamcinolone.

The Beta-RELIEVED trials were sponsored by Novartis, which markets canakinumab (Ilaris). Dr. Schlesinger said that she is a on the advisory board of Novartis, Enzyme Rx, Takeda, URL Pharma, and Savient. She is a consultant to and has received research grants from Novartis, and is on the speakers bureau of Takeda and Savient. Dr. So said that he is a consultant to Novartis, Bristol-Myers Squibb, Merck, Pfizer, and UCB Pharma. Dr. Khanna said that he is a consultant to Novartis, Takeda, Savient, and UCB Pharma.

LONDON – Among patients with giant cell arteritis, those in the lowest socioeconomic quarter of the population were more than three times as likely to have ischemic complications, based on data from 271 patients in England. The results were presented today.

Previous studies have shown a link between low socioeconomic status and carotid atherosclerosis. Studies of giant cell arteritis (GCA) have not controlled for socioeconomic status as a possible confounder, said Dr. Sarah Louise Mackie of the University of Leeds (England).

In an observational study of patients from eight recruitment centers in England, Dr. Mackie and her colleagues identified 271 confirmed cases of GCA.

Overall, 222 of 271 patients had ischemic complications. "The most striking finding was an association of ischemic complications with increasing Index of Deprivation 2007 (IMD2007) scores," with an odds ratio of 4.2 for the most-deprived quartile compared with the least-deprived quartile, Dr. Mackie noted. After controlling for a 30-day median duration of symptoms, the odds ratio for ischemic complications was 3.2 for the most-deprived quartile compared with the least-deprived quartile.

Ischemic complications were defined as lost or blurred vision; visual aura; diplopia; claudication of the jaw, tongue, or limb; scalp necrosis; or cerebral or myocardial ischemia.

Smoking was not associated with an increased risk of ischemic complications. Falling into the most socioeconomically deprived quartile was associated with a higher lifetime tobacco exposure and a lower prevalence of previously diagnosed polymyalgia rheumatica. However, neither of these factors appeared to affect the impact of socioeconomic deprivation on complications.

The adjusted odds ratio for the influence of hypertension was 1.6, and the adjusted odds ratio for the influence of atherosclerosis was 1.5. Neither of these conditions appeared to mediate the effect of socioeconomic deprivation on ischemic complications.

"This is a novel finding that requires replication," Dr. Mackie noted. Meanwhile, any public awareness campaign for GCA "should attempt to engage individuals in more deprived areas to encourage early presentation and prompt treatment," she said.

Dr. Mackie said she had no financial conflicts to disclose.

LONDON – Among patients with giant cell arteritis, those in the lowest socioeconomic quarter of the population were more than three times as likely to have ischemic complications, based on data from 271 patients in England. The results were presented today.

Previous studies have shown a link between low socioeconomic status and carotid atherosclerosis. Studies of giant cell arteritis (GCA) have not controlled for socioeconomic status as a possible confounder, said Dr. Sarah Louise Mackie of the University of Leeds (England).

In an observational study of patients from eight recruitment centers in England, Dr. Mackie and her colleagues identified 271 confirmed cases of GCA.

Overall, 222 of 271 patients had ischemic complications. "The most striking finding was an association of ischemic complications with increasing Index of Deprivation 2007 (IMD2007) scores," with an odds ratio of 4.2 for the most-deprived quartile compared with the least-deprived quartile, Dr. Mackie noted. After controlling for a 30-day median duration of symptoms, the odds ratio for ischemic complications was 3.2 for the most-deprived quartile compared with the least-deprived quartile.

Ischemic complications were defined as lost or blurred vision; visual aura; diplopia; claudication of the jaw, tongue, or limb; scalp necrosis; or cerebral or myocardial ischemia.

Smoking was not associated with an increased risk of ischemic complications. Falling into the most socioeconomically deprived quartile was associated with a higher lifetime tobacco exposure and a lower prevalence of previously diagnosed polymyalgia rheumatica. However, neither of these factors appeared to affect the impact of socioeconomic deprivation on complications.

The adjusted odds ratio for the influence of hypertension was 1.6, and the adjusted odds ratio for the influence of atherosclerosis was 1.5. Neither of these conditions appeared to mediate the effect of socioeconomic deprivation on ischemic complications.

"This is a novel finding that requires replication," Dr. Mackie noted. Meanwhile, any public awareness campaign for GCA "should attempt to engage individuals in more deprived areas to encourage early presentation and prompt treatment," she said.

Dr. Mackie said she had no financial conflicts to disclose.

LONDON – Among patients with giant cell arteritis, those in the lowest socioeconomic quarter of the population were more than three times as likely to have ischemic complications, based on data from 271 patients in England. The results were presented today.

Previous studies have shown a link between low socioeconomic status and carotid atherosclerosis. Studies of giant cell arteritis (GCA) have not controlled for socioeconomic status as a possible confounder, said Dr. Sarah Louise Mackie of the University of Leeds (England).

In an observational study of patients from eight recruitment centers in England, Dr. Mackie and her colleagues identified 271 confirmed cases of GCA.

Overall, 222 of 271 patients had ischemic complications. "The most striking finding was an association of ischemic complications with increasing Index of Deprivation 2007 (IMD2007) scores," with an odds ratio of 4.2 for the most-deprived quartile compared with the least-deprived quartile, Dr. Mackie noted. After controlling for a 30-day median duration of symptoms, the odds ratio for ischemic complications was 3.2 for the most-deprived quartile compared with the least-deprived quartile.

Ischemic complications were defined as lost or blurred vision; visual aura; diplopia; claudication of the jaw, tongue, or limb; scalp necrosis; or cerebral or myocardial ischemia.

Smoking was not associated with an increased risk of ischemic complications. Falling into the most socioeconomically deprived quartile was associated with a higher lifetime tobacco exposure and a lower prevalence of previously diagnosed polymyalgia rheumatica. However, neither of these factors appeared to affect the impact of socioeconomic deprivation on complications.

The adjusted odds ratio for the influence of hypertension was 1.6, and the adjusted odds ratio for the influence of atherosclerosis was 1.5. Neither of these conditions appeared to mediate the effect of socioeconomic deprivation on ischemic complications.

"This is a novel finding that requires replication," Dr. Mackie noted. Meanwhile, any public awareness campaign for GCA "should attempt to engage individuals in more deprived areas to encourage early presentation and prompt treatment," she said.

Dr. Mackie said she had no financial conflicts to disclose.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – An induction and maintenance treatment model works well for many patients with rheumatoid arthritis who start on potent, combined therapy very early in the course of their disease, based on 78-week follow-up of more than 200 patients in a randomized, controlled study.

The results showed that most patients who, within a few months of their onset of RA, began a regimen that combined the tumor necrosis factor (TNF) inhibitor adalimumab with methotrexate and who then reached a low level of disease activity after 22-26 weeks on the combined regimen could then switch to methotrexate monotherapy and remain at a low disease-activity state for the following year, Dr. Paul Emery and his associates reported in a poster at the annual European Congress of Rheumatology. Nearly half of the patients who began on the adalimumab plus methotrexate regimen reached a low disease activity state after 26 weeks.

The finding has important implications for the necessary duration of treatment with a TNF inhibitor, a member of the expensive class of biologic RA drugs.

"The key finding is that if you start patients on a biologic drug first, they do not take the biologic for life. You can probably stop [the biologic] in the majority of patients. The key is to treat patients when their disease is still completely reversible, hit them as hard as you can safely, and then hope to withdraw the biologic and [still] have a profound effect" on their disease that would not be possible if the biologic treatment was withheld until later, Dr. Emery said in an interview.

"It is an oncologic approach of induction and maintenance. The usual paradigm has been to use the cheap drugs" (disease-modifying antirheumatic drugs like methotrexate) first, and then, for the patients who failed to respond, to treat with a TNF inhibitor. But that approach delays treatment with the biologic until later in the course of RA. And at that point, withdrawal of the TNF inhibitor is harder because patients would then be left on just the drug (methotrexate) to which they had already failed to respond, he said.

Further analysis of the data collected in this study also holds the promise of finding demographic or clinical features to identify the patients who would best respond to initial combined therapy with a TNF inhibitor and methotrexate, followed by withdrawal of the biologic drug.

"We could use biomarkers to personalize [treatment], to target this approach to patients" who will likely succeed with induction and maintenance, said Dr. Emery, professor of rheumatology and head of the academic unit of musculoskeletal medicine at the University of Leeds (England). He plans to "define the subpopulation of very early RA patients who are capable of achieving and sustaining optimal therapeutic outcomes with early initiation of adalimumab and methotrexate, followed by biologic-free treatment.

Additional related issues that require further study include identifying what is the maximum level of disease activity that patients can have at the end of TNF-inhibitor treatment and still remain in a state of low disease activity. Another issue is whether patients who have disease recurrence when they are switched from combined treatment to methotrexate monotherapy can then restart the TNF inhibitor and still have a good response the second time.

The new analysis used data that were collected in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab Combination Therapy in Patients with Early RA) trial, conducted at 175 sites in 20 countries worldwide, including more than 50 U.S. centers. Between December 2006 and September 2010, the investigators randomized 1,032 patients with recently diagnosed RA to treatment with either adalimumab plus methotrexate or placebo plus methotrexate. Researchers administered 40 mg adalimumab once every other week, and they titrated methotrexate to a maximum dosage of 20 mg/week.

The analysis reported by Dr. Emery and his associates focused on patients who initially received the combined active treatment. Within that treatment group, they selected the 44% of patients who, at week 22-26, achieved a state of low disease activity, defined as a DAS28 (disease activity score based on a 28-joint count) less than 3.2. They randomized 102 of these patients to continue on methotrexate monotherapy and 105 patients to remain on combined therapy with methotrexate and adalimumab. These patients averaged 50 years of age, nearly three-quarters were women, 90% were white, and, at the time they entered the study, they had been diagnosed with RA for an average of 4 months.

The study’s primary end point was a DAS28-CRP (based on C-reactive protein) score of less than 3.2, and radiographic changes on the modified total Sharp score of 0.5 or less at week 78 of the study, after spending 1 year on the randomized, maintenance therapies. The percentage of patients who met this criterion was 55% in those who were treated with methotrexate monotherapy for 1 year and 70% among those who were kept on the dual regimen, a statistically significant difference.

But other, less stringent measures of disease activity showed fairly good maintenance with methotrexate monotherapy. For example, the percentage of patients at 78 weeks with low disease activity based on a DAS28-CRP score of less than 3.2 was 81% in the methotrexate monotherapy group and 91% among the patients on both active drugs. Of the patients on methotrexate alone, 84% had an SDAI (Simplified Disease Activity Index) of 11 or less at 78 weeks, as did 92% of those on methotrexate plus adalimumab. There was no radiographic progression in 81% of the patients in the monotherapy arm at 78 weeks and in 89% of the patients on both drugs. An ACR 50 (American College of Rheumatology scale showing a 50% improvement) response was recorded at 78 weeks in 80% of patients on methotrexate only and in 89% of patients on methotrexate plus adalimumab.

"On the whole, patients on methotrexate [monotherapy] did extremely well and maintained their responses," Dr. Emery said. These are "the first global, randomized, controlled data on discontinuation of a TNF inhibitor after successful achievement of stable, low disease activity. The data suggest that for a large proportion of very early RA patients, a 26-week course of adalimumab and methotrexate, followed by 52 weeks of methotrexate monotherapy, may be a viable option to allow for the achievement of good outcomes."

The study is funded by Abbott, the company that markets adalimumab (Humira). Dr. Emery said that he has received research support from and has been a consultant to Abbott, Bristol-Myers Squibb, Merck, Pfizer, and Roche.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – Prophylactic treatment with the potent interleukin-1 inhibitor rilonacept significantly reduced the incidence of acute gout flares triggered by the initiation of urate-lowering therapy, according to data from a global phase III study reported at the annual European Congress of Rheumatology.

Patients in the 16-week trial who were randomized to receive weekly subcutaneous injections of either 80 mg or 160 mg of rilonacept (Acralyst) at the outset of standard uric acid–reducing treatment with allopurinol had significantly fewer gout flares and significantly fewer days per flare than did patients randomized to placebo, said principal investigator Dr. Essack Mitha of Newtown Clinical Research in Johannesburg, South Africa.

Further, treatment with the fusion protein, which interrupts the inflammatory cascade by attaching to and neutralizing interleukin-1, demonstrated acceptable safety and tolerability, he said.

The findings are consistent with those of a sister phase III trial in North America reported at the 2010 annual meeting of the American College of Rheumatology, he said.

The phase III, double-blind Preventive Study Against Urate-Lowering Drug-Induced Gout Exacerbations (PRE-SURGE 2) was conducted in South Africa, Germany, and Asia, and included 248 patients with gout, serum uric acid levels of 7.5 mg/dL or higher, and a history of at least two gout flares in the prior year. All of the patients were initiated on 300 mg of allopurinol daily (except those with documented renal dysfunction, who were initiated on a lower dose), and subsequently titrated to achieve target urate levels of less than 6 mg/dL, Dr. Mitha stated.

After the initial allopurinol dose, which was continued for 20 weeks, including a 4-week safety follow-up period, patients were randomized to receive 16 weekly subcutaneous injections of placebo (82 patients), 80 mg of rilonacept with a double dosing on day 1 (82 patients), or 160 mg of rilonacept with a double dosing on day 1 (84 patients). During the study, nonsteroidal anti-inflammatory drugs and oral steroids were allowed for the treatment but not for prevention of gout flares, said Dr. Mitha.

"The primary end point was the mean number of gout flares per patient through week 16. The secondary end points were the proportion of patients experiencing two or more gout flares during this period and the number of flare-days per patient," he said, adding that safety and tolerability were also assessed.

At baseline, the characteristics of the predominantly male (93%) study population were similar across all three groups, with a mean age of 51 years, a mean serum uric acid level of 9.4 mg/dL, a mean of seven gout flares in the prior year, and a mean gout flare duration of 3.8 days. A similar number of patients in the placebo and rilonacept groups completed the treatment period, Dr. Mitha reported.

With respect to the primary end point, the mean number of gout flares per patient was 101 in the placebo group, 29 in the 80-mg rilonacept group, and 28 in the 160-mg rilonacept group, which represent a significant reduction in gout flares relative to placebo, said Dr. Mitha.

"Compared with placebo, the proportion of patients who experienced more than one gout flare through week 16 was reduced by 54% in the 80-mg group and 63% in the 160-mg group," he said. The respective reductions relative to placebo in the proportion of patients experiencing two or more flares were 74% and 82%. "The mean number of gout flare days per patient was also significantly lower in the rilonacept subjects, at 4.3 and 1.9 for the 80-mg and 160-mg groups, respectively, compared with 11.2 for placebo," and significantly fewer patients in the treatment arms had flares lasting 5 days or longer, he said.

In terms of adverse events, the overall incidence was similar across the groups, and although there were more injection-site reactions in the rilonacept groups, "the reactions were generally mild, and none of the patients withdrew for that reason," Dr. Mitha said. Three patients did withdraw from the higher-dose rilonacept group for other reasons – one each for neutropenia, gout flare, and gastric cancer – "but there were no deaths and no serious adverse events related to the product," he stressed.

Together with the results of the North American PRE-SURGE 1 trial, the findings of this study are an important step in the clinical development program for rilonacept, which the U.S. Food and Drug Administration approved in February 2008 for the treatment of cryopyrin-associated periodic syndromes and Muckle-Wells syndrome in adults and children older than 12 years.

"Our results suggest that concomitant use of rilonacept during the first several months of allopurinol therapy may help avoid the acute gout flares that make it difficult for patients to maintain urate-lowering therapy," according to Dr. Mitha. Currently, standard practice includes the use of colchicine or anti-inflammatory drugs to reduce the risk of flares associated with early allopurinol, but the gastrointestinal side effects associated with colchicine in particular can be prohibitive, he said.

Because rilonacept is "very expensive" compared with standard treatment for acute gout flares, studies looking at the relative efficacy of the various treatment options are warranted before the drug should be widely used for this indication, Dr. Mitha stressed.

Dr. Mitha and his coinvestigators disclosed receiving grant/research support from Regeneron Pharmaceuticals, which manufactures rilonacept.

LONDON – The reasons why fewer black than white patients undergo knee replacement as a treatment option for end-stage osteoarthritis remain elusive.

According to the findings of a 725-patient study, women and blacks with knee osteoarthritis (OA) were less willing than men or their white counterparts to consider having total knee replacement (TKR) surgery.

Black patients were also found to be less aware of the benefits of joint replacement and had worse expectations of the outcome than did white patients.

Despite a number of sociocultural differences, however, it is not clear why the uptake of TKR differs among ethnic groups.

"We know that joint replacement is an effective – actually the only effective – intervention for end-stage osteoarthritis," said study author Dr. C. Kent Kwoh, who is professor of medicine, epidemiology and clinical and translational science at the University of Pittsburgh and chief of the rheumatology section at VA Pittsburgh Healthcare System.

"The problem is that there have been many studies that have shown there are disparities in joint replacement; [blacks] get hip and knee replacement much less often than do whites," Dr. Kwoh added in an interview during a poster session at the annual European Congress of Rheumatology. "The question is, Why?"

Previous research has shown that even when faced with very severe and painful OA and a physician recommendation for TKR, black patients are less willing than whites to consider this an option.

The present study was in a much larger community-based sample than has been the case in past investigations, said Dr. Kwoh, and it aimed to identify more specific factors and patient attitudes that might influence the decision to undergo TKR.

Using a cross-sectional survey design, the investigators recruited patients aged 50 years or older who had chronic, frequent knee pain and radiographic evidence of OA.

The study population consisted of 234 black and 491 white patients, with mean respective ages of 58 years and 68 years (P less than .0004).

In addition to being younger, black patients tended to have worse knee pain, with higher total WOMAC (Western Ontario and McMaster Universities) osteoarthritis index scores (54 vs. 43), and OA Pain Assessment scores for constant (7 vs. 11) and intermittent (14 vs. 11) pain than white patients (P less than .0004 for all comparisons).

"There were differences in a number of [other] variables [between whites and blacks], such as income, employment status, education, access to insurance, expectations of outcome, trust in the health system, and religiosity, that may impact the choice for joint replacement" Dr. Kwoh observed.

However, putting all of these variables into a multivariate model didn’t seem to fully explain the disparity in TKR acceptance between the two groups.

The adjusted odds ratio for willingness to undergo TKR was 0.38 comparing black vs. white patients (95% confidence interval, 0.19-0.74; P = .005) and 2.52 for male vs. female sex (95% CI, 1.37-4.66; P = .003).

"We’re left a little bit puzzled at this point," Dr. Kwoh admitted. "Our other studies have shown differences in expectations; that is, if you have worse expectations, you were less likely to consider joint replacement."

In that previous work, however, an adjustment of the findings according to patient expectations seemed to take care of the difference in willingness. "In this study, we weren’t able to show that," Dr. Kwoh said. "So maybe there are other, unmeasured confounders that we have to address."

As to where these findings leave the practicing physician who advises patients, Dr. Kwoh noted that patient education is important and that patients really need to have a good understanding of the risks and benefits.

"Joint replacement is effective, we know that it works very well, it has low morbidity and low mortality, and so patients who really need it should avail themselves to it," Dr. Kwoh advised.

Dr. Kwoh stated that he had no conflicts of interest. The study was funded by the University of Pittsburgh Multidisciplinary Clinical Research Center for Rheumatic and Musculoskeletal Diseases.

LONDON – The reasons why fewer black than white patients undergo knee replacement as a treatment option for end-stage osteoarthritis remain elusive.

According to the findings of a 725-patient study, women and blacks with knee osteoarthritis (OA) were less willing than men or their white counterparts to consider having total knee replacement (TKR) surgery.

Black patients were also found to be less aware of the benefits of joint replacement and had worse expectations of the outcome than did white patients.

Despite a number of sociocultural differences, however, it is not clear why the uptake of TKR differs among ethnic groups.

"We know that joint replacement is an effective – actually the only effective – intervention for end-stage osteoarthritis," said study author Dr. C. Kent Kwoh, who is professor of medicine, epidemiology and clinical and translational science at the University of Pittsburgh and chief of the rheumatology section at VA Pittsburgh Healthcare System.

"The problem is that there have been many studies that have shown there are disparities in joint replacement; [blacks] get hip and knee replacement much less often than do whites," Dr. Kwoh added in an interview during a poster session at the annual European Congress of Rheumatology. "The question is, Why?"

Previous research has shown that even when faced with very severe and painful OA and a physician recommendation for TKR, black patients are less willing than whites to consider this an option.

The present study was in a much larger community-based sample than has been the case in past investigations, said Dr. Kwoh, and it aimed to identify more specific factors and patient attitudes that might influence the decision to undergo TKR.

Using a cross-sectional survey design, the investigators recruited patients aged 50 years or older who had chronic, frequent knee pain and radiographic evidence of OA.

The study population consisted of 234 black and 491 white patients, with mean respective ages of 58 years and 68 years (P less than .0004).

In addition to being younger, black patients tended to have worse knee pain, with higher total WOMAC (Western Ontario and McMaster Universities) osteoarthritis index scores (54 vs. 43), and OA Pain Assessment scores for constant (7 vs. 11) and intermittent (14 vs. 11) pain than white patients (P less than .0004 for all comparisons).

"There were differences in a number of [other] variables [between whites and blacks], such as income, employment status, education, access to insurance, expectations of outcome, trust in the health system, and religiosity, that may impact the choice for joint replacement" Dr. Kwoh observed.

However, putting all of these variables into a multivariate model didn’t seem to fully explain the disparity in TKR acceptance between the two groups.

The adjusted odds ratio for willingness to undergo TKR was 0.38 comparing black vs. white patients (95% confidence interval, 0.19-0.74; P = .005) and 2.52 for male vs. female sex (95% CI, 1.37-4.66; P = .003).

"We’re left a little bit puzzled at this point," Dr. Kwoh admitted. "Our other studies have shown differences in expectations; that is, if you have worse expectations, you were less likely to consider joint replacement."

In that previous work, however, an adjustment of the findings according to patient expectations seemed to take care of the difference in willingness. "In this study, we weren’t able to show that," Dr. Kwoh said. "So maybe there are other, unmeasured confounders that we have to address."

As to where these findings leave the practicing physician who advises patients, Dr. Kwoh noted that patient education is important and that patients really need to have a good understanding of the risks and benefits.

"Joint replacement is effective, we know that it works very well, it has low morbidity and low mortality, and so patients who really need it should avail themselves to it," Dr. Kwoh advised.

Dr. Kwoh stated that he had no conflicts of interest. The study was funded by the University of Pittsburgh Multidisciplinary Clinical Research Center for Rheumatic and Musculoskeletal Diseases.

LONDON – The reasons why fewer black than white patients undergo knee replacement as a treatment option for end-stage osteoarthritis remain elusive.

According to the findings of a 725-patient study, women and blacks with knee osteoarthritis (OA) were less willing than men or their white counterparts to consider having total knee replacement (TKR) surgery.

Black patients were also found to be less aware of the benefits of joint replacement and had worse expectations of the outcome than did white patients.

Despite a number of sociocultural differences, however, it is not clear why the uptake of TKR differs among ethnic groups.

"We know that joint replacement is an effective – actually the only effective – intervention for end-stage osteoarthritis," said study author Dr. C. Kent Kwoh, who is professor of medicine, epidemiology and clinical and translational science at the University of Pittsburgh and chief of the rheumatology section at VA Pittsburgh Healthcare System.

"The problem is that there have been many studies that have shown there are disparities in joint replacement; [blacks] get hip and knee replacement much less often than do whites," Dr. Kwoh added in an interview during a poster session at the annual European Congress of Rheumatology. "The question is, Why?"

Previous research has shown that even when faced with very severe and painful OA and a physician recommendation for TKR, black patients are less willing than whites to consider this an option.

The present study was in a much larger community-based sample than has been the case in past investigations, said Dr. Kwoh, and it aimed to identify more specific factors and patient attitudes that might influence the decision to undergo TKR.

Using a cross-sectional survey design, the investigators recruited patients aged 50 years or older who had chronic, frequent knee pain and radiographic evidence of OA.

The study population consisted of 234 black and 491 white patients, with mean respective ages of 58 years and 68 years (P less than .0004).

In addition to being younger, black patients tended to have worse knee pain, with higher total WOMAC (Western Ontario and McMaster Universities) osteoarthritis index scores (54 vs. 43), and OA Pain Assessment scores for constant (7 vs. 11) and intermittent (14 vs. 11) pain than white patients (P less than .0004 for all comparisons).

"There were differences in a number of [other] variables [between whites and blacks], such as income, employment status, education, access to insurance, expectations of outcome, trust in the health system, and religiosity, that may impact the choice for joint replacement" Dr. Kwoh observed.

However, putting all of these variables into a multivariate model didn’t seem to fully explain the disparity in TKR acceptance between the two groups.

The adjusted odds ratio for willingness to undergo TKR was 0.38 comparing black vs. white patients (95% confidence interval, 0.19-0.74; P = .005) and 2.52 for male vs. female sex (95% CI, 1.37-4.66; P = .003).

"We’re left a little bit puzzled at this point," Dr. Kwoh admitted. "Our other studies have shown differences in expectations; that is, if you have worse expectations, you were less likely to consider joint replacement."

In that previous work, however, an adjustment of the findings according to patient expectations seemed to take care of the difference in willingness. "In this study, we weren’t able to show that," Dr. Kwoh said. "So maybe there are other, unmeasured confounders that we have to address."

As to where these findings leave the practicing physician who advises patients, Dr. Kwoh noted that patient education is important and that patients really need to have a good understanding of the risks and benefits.

"Joint replacement is effective, we know that it works very well, it has low morbidity and low mortality, and so patients who really need it should avail themselves to it," Dr. Kwoh advised.

Dr. Kwoh stated that he had no conflicts of interest. The study was funded by the University of Pittsburgh Multidisciplinary Clinical Research Center for Rheumatic and Musculoskeletal Diseases.